The pHi (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pHi. Sensors of pHi include ion transport systems which control intracellular Ca2+ gradients and link changes in pHi to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca2+-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2–S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pHi on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2–S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2–S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2–S100A10 might have consequences for their functions as membrane organizers and channel modulators.
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January 2008
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Research Article|
December 11 2007
Annexins sense changes in intracellular pH during hypoxia
Katia Monastyrskaya;
Katia Monastyrskaya
1
*Department of Cell Biology, Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland
1Correspondence may be addressed to either of these authors (email monastyk@ana.unibe.ch or draeger@ana.unibe.ch)
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Fabian Tschumi;
Fabian Tschumi
*Department of Cell Biology, Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland
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Eduard B. Babiychuk;
Eduard B. Babiychuk
*Department of Cell Biology, Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland
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Deborah Stroka;
Deborah Stroka
†Department of Clinical Research, Medical Faculty, University of Bern, 3010 Bern, Switzerland
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Annette Draeger
Annette Draeger
1
*Department of Cell Biology, Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland
1Correspondence may be addressed to either of these authors (email monastyk@ana.unibe.ch or draeger@ana.unibe.ch)
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Publisher: Portland Press Ltd
Received:
August 14 2007
Revision Received:
September 06 2007
Accepted:
September 10 2007
Accepted Manuscript online:
September 10 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 409 (1): 65–75.
Article history
Received:
August 14 2007
Revision Received:
September 06 2007
Accepted:
September 10 2007
Accepted Manuscript online:
September 10 2007
Citation
Katia Monastyrskaya, Fabian Tschumi, Eduard B. Babiychuk, Deborah Stroka, Annette Draeger; Annexins sense changes in intracellular pH during hypoxia. Biochem J 1 January 2008; 409 (1): 65–75. doi: https://doi.org/10.1042/BJ20071116
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